Inflammation is the body's response to injury, infection, or molecules perceived by the immune system as foreign. Inflammation is characterized by pain, swelling and altered function of the affected tissue. Although the ability to mount an inflammatory response is essential for survival, the ability to control inflammation is also necessary for health. Inflammatory diseases are characterized by activation of the immune system in a tissue or an organ to abnormal levels that may lead to abnormal function and/or disease in the tissue or organ.
Inflammatory diseases are a major cause of morbidity and mortality throughout the world. They affect various organs and tissues such as blood vessels, heart, brain, nerves, joints, skin, the lung, eye, gastrointestinal tract, kidneys, thyroid, adrenals, the pancreas, liver, and muscle. Treatments of inflammatory diseases have drawn a great deal of attention from the pharmaceutical industry. A recurrent theme in discussions of treatment options for inflammatory disorders is the inadequacy of the standard of care. Management and treatments are seeing improvements but there are no cures. The most common approach to treating inflammatory disorders in the last decade has addressed the pro-inflammatory role of cytokines with compounds that bind to these molecules or their receptors.
Despite recent advances, current therapies for inflammatory diseases still entail alleviating symptoms and reducing inflammation with non-specific drugs, slowing disease progression with disease-modifying agents, and improving the quality of life with lifestyle modifications, all while contending with side effects and resistance to medications. Better treatment options with less potential for side effects are needed.
Because the outcome of treatment depends on a proper diagnosis, it is important to have proper tests to diagnose inflammatory diseases and to monitor the treatment of those diseases. A proper diagnosis permits a physician to institute proper and timely therapy. Proper monitoring of treatment allows the physician to decide on the course of treatment and to advise patients and their families about the expected disease course. Thus, there is also a strong incentive to identify new improved tests and approaches to diagnose and to evaluate treatments of inflammatory diseases.
Gelsolin, first discovered as an intracellular actin-binding protein involved in cell motility (Yin, H. L. & Stossel, T. P. (1979) Nature 281, 583-6), has been recently implicated in a number of diseases. While the true function of plasma gelsolin is not known, clinical and animal studies have shown that depletion of plasma gelsolin by injury and inflammation is associated with adverse outcomes. The proposed mechanism of gelsolin depletion is that it binds abundant actin in cells exposed by tissue breakdown. More recently, gelsolin was found to bind bioactive inflammatory mediators, lysophosphatidic acid, diadenosine phosphate, Aβ peptide (a peptide implicated in the pathogenesis of Alzheimer's disease), platelet-activating factor and possibly others.